This is a new application for a K01 award for Dr. Julia Simard, an epidemiologist at Stanford University School of Medicine, who plans a research program focusing on adverse reproductive and birth outcomes of women with systemic lupus erythematosus (SLE). Although Dr. Simard has a strong background in epidemiology and registry research, she requires skills in three additional areas to achieve her long-term goals: (1 in-depth knowledge of basic and clinic science of the immune system and the other organ systems affected by systemic autoimmune diseases; (2) advanced training in reproductive and perinatal epidemiology; and (3) proficiency in advanced statistical techniques for meta-analysis, research synthesis using Bayesian methods, and multivariate modeling. To build this foundation, Dr. Simard and her mentors have created a multi-disciplinary career development plan that includes the following elements: (1) advanced coursework in clinical medicine, immunology, pathology and maternal-fetal medicine, with additional individual mentoring in basic and clinical immunology by Drs. Utz and Salmon; (2) direct training in reproductive and perinatal epidemiology through one-on-one tutorials and research supervision by Drs. Druzin and Salmon; and (3) advanced coursework in research synthesis, Bayesian methods and multivariate analyses, complemented by mentored directed readings with Drs. Goodman and Nelson. Formal coursework and mentoring at Stanford University will be supplemented with short courses and attendance at national conferences related to reproductive and perinatal epidemiology, rheumatology, and immunology. Integrating this substantive and methodological knowledge with her mentored research project will substantially augment Dr. Simard's research capabilities and enable her to lead an independent multidisciplinary research program. For her K01 mentored research project, Dr. Simard will carry out a linkage of Swedish population-based register data to create one of the world's largest cohorts of patients with SLE matched to individuals from the general population as a comparator group. These data will then be used to assess risks and outcomes in mothers and offspring, and to investigate the aspects of SLE pathogenesis that drive these risks. In Aim 1, Dr. Simard will conduct a cohort study using prospectively collected linked national data from at least 1000 SLE pregnancies and over 40,000 pregnancies among women sampled from the general population to assess maternal risks of pregnancy including preterm labor, late-term pregnancy loss, pre-eclampsia, stroke, and death. Adverse outcomes associated with SLE will be investigated to identify potential predictors and clinically modifiable factors. In Aim 2, Dr. Simard will use the same population-based database to identify adverse fetal and childhood outcomes associated with SLE pregnancy. In addition to identifying subsets of women to monitor closely for targeted interventions, Dr. Simard's mentored research project is expected to yield information that will enable clinicians to better counsel women with SLE regarding pregnancy risks, and could lead to important new insights about the pathophysiology of SLE.